Flashcards in 2/24 Deck (75):
What causes inc. toxicity for all class 1 (Na channel blocker) drugs?
-further depolarizes the cell.
How does cell get out of refractory phase and back to ready phase?
-repolarization, which depends on K efflux.
Hypoxic tissue: most cardiac myocytes will have Na channels in which phase?
-which class of Na blockers targets ischemic tissue?
-they're loaded cations cuz they're hypoxic.
-that means they're slightly depolarized
-that means they're in refractory state, H gate closed.
-Class 1B's target refractory Na channels, aka ischemic tissue.
Mnemonic for class 1a
Double Quarter Pounder
Class 1a mechanism
-what happens to the ECG?
1) Blocks open/ready Na channels => dec. slope phase 0
2) Blocks K channels => dec. slope phase 3
-inc. ERP (making it take longer to repolarize and get rid of H-gate)
*total effect = inc. QT interval (systole) on ECG.
*dec. slope of phase 0 = widened QRS.
*dec. slope of phase 3 = widened T wave.
-what does it depend on?
-effective refractory period is when the H-gate is close, so the Na channel is refractory. It can not be opened no matter what.
-The H-gate is voltage controlled
-It shuts after the cell depolarizes, and it opens back up once the cell is sufficiently repolarized.
*The potassium efflux is the main determinant of the ERP!
-aka the slope of phase 3!
Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT.
-mostly used for afib.
-what tissue is it mostly targeting?
-cardiac myocytes and conducting system but NOT the nodal tissue.
-nodal tissue phase 0 relies on Ca influx, not Na influx.
Toxicity of Class 1a
-Cinchonism (headache, tinnitus with quinidine)
*quinidine has anti-muscarinic & anti-alpha1
-SLE-like syndrome (procainamide)
-heart failure (disopyramide)
-torsades de pointes due to QT interval.
Lettuce Tomato Mayo Pickles
-Lidocaine, tocainide, mexiletine, phenytoin
*everything except the onions.
1)Blocks slow Na channels that maintain ST segment/plateau/phase2 = dec. phase 2 length.
2)Blocks refractory Na channels, preventing them from being reactivated= inc. diastolic time and reducing systolic time (more time btwn APs).
*overall = reduce APD & HR.
Class 1a & 1b
-targets which type of tissue
-cardiac myocytes + conducting system
-targets which type of tissue?
-Acute ventricular arrhythmias (especially post-MI)
*IB is Best post-MI. Stops the ischemic regions from becoming ectopic foci by slowing them down.
*Class 1a slow down too, but class 1bs target ischemic cells.
*remember, phenytoin used as anti-convulsant.
More Fries Please
-moricizine, flecainide, propafenone.
-significantly prolongs refractory period in AV node.
-minimal effect on APD.
-blocks all Na channels.
-Slows phase 4
-Dec. SA & AV nodal activity by dec. cAMP
-Dec. cAMP => dec. Ca currents
-inc. PR interval: AV node very sensitive.
*dec Ca currents: influx into cell as well as putting Ca back into SR. Longer it takes to put Ca back into SR, the longer it takes to repolarize, and the longer it takes for phase 4 to kick in.
Do you use beta-blockers on diabetics?
Do you use beta-blockers on cocaine users?
-no b/c tachy is one of signs of hypoglycemia and you will block that.
-Dont give cocaine users beta-blockers. Risk of unopposed α-adrenergic receptor agonist activity
-treat overdose w/what?
-metoprolol = dyslipidemia
-Propranolol can exacerbate vasospasm in Prinzmetal angina.
-treat OD w/glucagon
Potassium channel blocker
-less K efflux = longer phase 3 = longer it takes to repolarize = longer it takes for H-gates on Na channels to open up = longer it takes for next AP.
-inc. QT interval
Potassium channel blocker
K IS BAD
Potassium channel blockers
*anything that prolongs QT interval can cause torsades.
Sotalol—torsades de pointes, excessive β blockade.
Ibutilide—torsades de pointes.
Amiodarone—pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine by weight), corneal deposits, skin deposits
(blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF).
What is special about amiodarone?
Amiodarone has class I, II, III, and IV effects and
alters the lipid membrane.
Ca channel blockers
-Constipation, flushing, edema, hyperprolactinemia, CV effects (CHF, AV block, sinus node depression).
Ca channel blockers
1)Block Ca influx: slows phase 0 = QRS = depol.
2)Block Ca sequestration back into SR = slows phase 3 = repolarization.
Ca channel blockers
Prevention of nodal arrhythmias (e.g., SVT), rate control in atrial fibrillation.
-inc. K efflux = hyperpolarizes cell which dec. rate of depolarization (Ca influx).
-acts on phase 4, slows it down. Reduces the rate of spont. depolarization in nodal tissue.
Whats the DOC for diagnosing/abolishing supraventricular tachycardia?
What blocks the effects of adenosine?
-Theophylline and caffeine.
-They antagonize the adenosine receptor.
-Effective in torsades de pointes and digoxin toxicity.
-structurally similar to Ca so competes w/Ca but has none of calcium's effects.
-torsades is essentially too long of a QT interval = too much systole = too much contraction. Makes sense that blocking Ca would help this.
-same w/digoxin that is a positive inotrope.
Which classes of AAs prolong the QT interval?
Class 1a & class 3
-both block K efflux.
Another name for torsades de pointes?
Which drug that prolongs QT interval has lowest risk of leading to torsades?
In simple terms, what does adenosine do?
Causes transient conduction delay through AV node.
Why dont beta-blockers prolong QT interval if they're prolonging conduction thru AV node (via reducing Ca current).
B/c the QT interval is ventricular contraction/systole.
-QT interval encompasses ventricular depol. and repol.
-SA and AV node stuff isn't in the QT interval.
-thats why beta-blockers and calcium channel blockers dont alter QT interval, b/c they mostly affect nodal tissue.
ERP relationship w/QT interval
-ERP prolonged in AV node = prolonged PR interval
-ERP prolonged in ventricular cells = prolonged QT interval
Intrinsic = PTT = SEC = HEP
*intrinsic has more factors than extrinsic & PTT has more letters than PT.
Extrinsic = PT = TT = Warfarin
-Put for "7s" next to each other and you get an X for extrinsic.
Deep tissue bleeding think:
-ie. bleeding s/p tooth extractino or hemarthroses
Mucocutaneous bleeding think:
-ie. epistaxis, petechiae, menorrhagia
Is mennorhagia a sign of platelet or coag problem?
-its mucocutaneous bleeding (like epistaxis) so its a platelet problem.
-causes hypercoag state that can lead to spont. abortion.
which platelet receptor binds vWF
vWF relation to factor 8
-carrier for factor 8, inc. its half life in plasma.
-in absence of vWF, factor 8 rapidly degraded in circulation.
what converts fibrinogen to fibrin?
thrombin (factor 2a)
*thrombin forms a thrombus.
muscle pain w/exercise that remits w/rest.
-esp. if its a certain region.
-almost always due to atherosclerosis.
Medial band-like calcifications
monckeberg's medial calcific sclerosis
-dont narrow the vessel lumen.
what does bundle branch conductivity dictate?
how wide the QRS complex is.
-widened when there is a bundle branch block.
-it doesn't affect the contraction rate.
Is there an inc or dec in BP in CHF?
-this is fundamental to the entire pathology.
what kind of cardiomyopathy does doxorubicin,daunorubicin cause?
-how do u prevent this cardiotoxicity?
-dilated cardiomyopathy (free radical dmg)
-dexrazoxane (iron chelator, prevents formation of oxygen free radicals)
-alternate way to measure JVD
what kind of cardiomyopathy does radiation lead to?
-can also lead to pericardial fibrosis
QRS complex duration
sample only looking at inpatients.
-type of selection bias
Do varicose veins lead to pulm. embolism?
Not usually b/c varicose veins are typically the superficial veins. They can thrombose but only deep vein thromboses lead to pulm. embolism.
-surgical removal of plaque from an artery thats become narrowed or blocked.
irreversible competitive antagonist
-hows the curve look?
-decreased efficacy, same as a noncompetitive inhibitor.
-PDE3 inhibitor = inc. cAMP
-inhibit platelet aggregation & vasodilate.
*selectively vasodilates coronary vessels.
Which vessels does adenosine selectively dilate?
-pain radiating to neck or shoulder
-pleuritic pain = suggests inferior pericardium is involved since its adjacent to phrenic nerve.
-post. pericardium could be involved.
-presence of protein or bile salts in urine.
Aldo levels in nephrotic syndrome
-high. losing fluid to interstitial compartment b/c of low albumin in plasma.
-leads to high renin system.
L-type Ca channels:
-what causes them to close?
-where are they located?
-whats another name for them?
-They're time dependent. Close automatically.
*ryanodine receptors are on SR.
Gs & cAMP & PKA action on calcium channels.
-L-type calcium channels (DHP channels) & ryanodine channels: they have inc. permeability to calcium when they're phosphorylated.
-thats how PKA & Gs pathway leads to inc. inotropy.
Most common cause of xanthelasma
-LDL receptor abnormality.
-2a- familial hypercholesterolemia.
Does international normalized ratio refer to PT or PTT
-you know this b/c pts on warfarin use it.
-you keep track of warfarin status by measuring PT.
Which artery mostly commonly has atherosclerosis?
abdominal aorta > coronary > popliteal > internal carotids > circle of willis
In the carotid system, which region is most prone to atherosclerosis?
What murmur does endocarditis usually cause?
-mitral or tricuspid.
-what heart pathology does it cause?
myocarditis which can progress to dilated cardiomyopathy.
ACE inhibitors: what causes the angioedema?
accumulation of kinin
-bradykinin = a kinin. Its a potent vasodilator.
Whats the myocardium look like in the first 4 hours following MI?
-how long does it take for granulation tissue to show up?
-first 4 horus = normal
-10-14 days if when you see granulation tissue.
How long after MI do you start seeing early coag necrosis. Hyper-eosinophilia, edema, hemorrhage, & wavy fibers.
-4-12 hours in.